Back to resultsQuick Start Durvalumab Following Chemoradiation for Stage III Nonsmall Cell Lung Cancer
Primary Purpose
Nonsmall Cell Lung Cancer Stage III, Unresectable Non-Small Cell Lung Carcinoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Durvalumab
the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30)
COPD Assessment Test (CAT)
Modified Medical Research Council (mMRC) dyspnea scale
Sponsored by
About this trial
This is an interventional treatment trial for Nonsmall Cell Lung Cancer Stage III
Eligibility Criteria
Inclusion Criteria: Histological or cytological documentation of nonsmall cell lung cancer that is Stage III according to the American Joint Committee on Cancer Staging Manual, 8th Edition (2017). Unresectable or medically inoperable as determined by the investigator. The participant has definitive radiation therapy (e.g., 54 Gy to 66 Gy in 30 to 35 fractions) for lung cancer that is either (a) planned to start within the next 28 days, or (b) currently being administered, or (c) has been completed within the last 14 days. Platinum-based chemotherapy for lung cancer that is either (a) planned to start within the next 28 days, (b) currently being administered, or (c) has been completed within the last 14 days. Chemotherapy must be for at least two cycles and be administered either before radiation therapy ("induction" or "sequential") or during radiation therapy ("concurrent"). Consolidation Durvalumab is planned for nonsmall cell lung cancer after radiation and chemotherapy. Eighteen years old or greater. ECOG performance status of 0-2. Life expectancy of greater than three months. Patients with sexual relationships in which either they or their partner may become pregnant must use contraception during the study treatment period. Ability to understand and be willing to sign an IRB-approved informed consent document directly or via a legally authorized representative. Exclusion Criteria: Uncontrolled respiratory symptoms (i.e., cough, dyspnea, fevers, chest pain, or an increase from baseline oxygen requirements) that are interfering with activities of daily living. Nonsmall cell lung cancer is known to have progressed during radiation therapy. Nonsmall cell lung cancer is known to have a tumor with a mutation in EGFR associated with sensitivity to first-line therapy with a tyrosine kinase inhibitor (i.e., Ex19del, L858R, EGFR S768I, L861Q, or G719X). If not already known, testing for EGFR mutations is not required for study enrollment. Prior exposure to an immune checkpoint inhibitor targeting CTLA-4, PD-1, or PD-L1. Active autoimmune disease requiring systemic immunosuppression at the time of enrollment. History of autoimmune pneumonitis requiring high-dose systemic steroids (equivalent prednisone >20 mg/day for more than one week). Uncontrolled intercurrent illness includes ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients who are pregnant or breastfeeding.
Sites / Locations
- Wake Forest Baptist Comprehensive Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Quick Start Durvalumab
Arm Description
Standard of care test and procedures for cancer treatments along with Durvalumab treatment at physician's discretion
Outcomes
Primary Outcome Measures
Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Early Initiation (1-14 days)
Fidelity is defined as a dichotomous composite indicator (yes/no) that describes whether the patient received very early (1-7 days) initiation of Durvalumab as per protocol with all four of the following criteria having been met: (i) CT chest obtained after the last day of radiation therapy and before the first infusion of Durvalumab, (ii) first infusion within 14 days of completing radiation therapy, (iii) second and third doses received within 63 days of the first dose, and (iv) all infusions at least 28 days apart.
Secondary Outcome Measures
Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Very Early (1-7 days)
Fidelity is defined as a dichotomous composite indicator (yes/no) that describes whether the patient received very early (1-7 days) initiation of Durvalumab as per protocol with all four of the following criteria having been met: (i) CT chest obtained after the last day of radiation therapy and before the first infusion of Durvalumab, (ii) first infusion within 7 days of completing radiation therapy, (iii) second and third doses received within 63 days of the first dose, and (iv) all infusions at least 28 days apart.
Number of Barriers to Initiation of Durvalumab - Very Early (Days 1-7)
Descriptive frequencies of participant survey answers will be examined to conduct qualitative analyses and determine appropriate categories of answers on the free text responses. We will examine barriers/obstacles for everyone in the sample, even those who achieve fidelity; such patients could have experienced delays even if they were still able to achieve fidelity. We will stratify answers/responses by fidelity status.
Number of Barriers to Initiation of Durvalumab - Early (Days 8-14)
Descriptive frequencies of participant survey answers will be examined to conduct qualitative analyses and determine appropriate categories of answers on the free text responses. We will examine barriers/obstacles for everyone in the sample, even those who achieve fidelity; such patients could have experienced delays even if they were still able to achieve fidelity. We will stratify answers/responses by fidelity status.
Incidences of All Adverse Events
Adverse events, serious adverse events and immune-related adverse events will be tabulated by fidelity status (1-7 days vs. 8-14 days vs. neither) using National Cancer Institute Common Terminology Criteria, version 5.0.
Number of Participants Who Have Immune-Mediated Pneumonitis - Early Fidelity (1-14 days)
Participants with early (1-14 days) fidelity who have immune-mediated early-onset pneumonitis will be estimated and statistically compared in a one-sample test of proportions.
Number of Participants Who Have All-Cause Pneumonitis - Early Fidelity (1-14 days)
Participants with all-cause early-onset pneumonitis among those with early (1-14 days) fidelity and statistically compare it, using a one-sample test of proportions.
Number of Participants to Discontinue Durvalumab Due to Adverse Events
Participants with early fidelity who discontinue Durvalumab at any point due to an adverse event of any cause and compare it using a one-sample test of proportions.
Overall Survival
Using Kaplan-Meier life table methods, overall survival is defined as the number of participants alive at 12 months after the first dose of Durvalumab.
Progression-Free Survival
Using Kaplan-Meier methods, progression-free survival is defined as the number of participants alive and without disease progression as documented by the treating provider at 12 months after the first dose of Durvalumab.
Response Rate
Best objective response rate (ORR) to Durvalumab is defined by either a complete response (CR) or partial response (PR) as per RECIST 1.1 criteria by investigator assessment and confirmed on at least two sequential imaging studies that are at least four weeks apart
Change in Patient-Reported Outcomes Scores (PROs) - European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Version 3
The change in PROs scores from baseline to week 12 using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither). Scale scores range from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
Change in Patient-Reported Outcomes Scores (PROs) - Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) Questionnaire
The QLQ-LC13 includes questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea and site specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. The change in PROs scores from baseline to week 12 using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither). Scale scores range from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
Change in Respiratory Patient Reported Outcomes (PROs) - COPD Assessment Test (CAT)
The COPD Assessment Test (CAT) is a questionnaire for people with Chronic Obstructive Pulmonary Disease (COPD). It is designed to measure the impact of COPD on a person's life and how this changes over time. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD. The change in PROs scores using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither).
Change in Respiratory Patient Reported Outcomes (PROs) - Modified Medical Research Council (mMRC) Dyspnea Scale
The mMRC (Modified Medical Research Council) Dyspnea Scale is used to assess the degree of baseline functional disability due to dyspnea.The mMRC breathlessness scale ranges from grade 0 to 4 with grade 4 indicating a higher level of respiratory disease severity.
Full Information
NCT ID
NCT05696782
First Posted
January 12, 2023
Last Updated
August 8, 2023
Sponsor
Wake Forest University Health Sciences
1. Study Identification
Unique Protocol Identification Number
NCT05696782
Brief Title
Quick Start Durvalumab Following Chemoradiation for Stage III Nonsmall Cell Lung Cancer
Official Title
Phase II Pilot Study of Quick Start Durvalumab Following Chemoradiation for Stage III Nonsmall Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 26, 2023 (Actual)
Primary Completion Date
May 2025 (Anticipated)
Study Completion Date
July 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This research study aims to determine what effects (good and bad) Durvalumab has on participants and their cancer with a "quick start" of Durvalumab within 14 days of finishing chemotherapy and radiation. The study will also determine the logistic barriers to the quick start of Durvalumab.
Detailed Description
Primary Objective: Assess the treatment fidelity for early Durvalumab initiation (i.e., within 14 days after the last day of radiation therapy) following chemoradiation for Stage III, unresectable nonsmall cell lung cancer.
Secondary Objectives:
Assess the treatment fidelity for very early Durvalumab initiation (i.e., within seven days after the last day of radiation therapy) following chemoradiation for Stage III, unresectable nonsmall cell lung cancer.
Assess barriers to earlier Durvalumab initiation following chemoradiation for Stage III nonsmall cell lung cancer.
Describe the toxicity of Durvalumab when initiated quickly after chemoradiation for Stage III nonsmall cell lung cancer as compared to historical controls.
Describe the efficacy of Durvalumab when initiated quickly after chemoradiation for Stage III nonsmall cell lung cancer as compared to historical controls.
Describe the patient-reported outcomes of Durvalumab when initiated quickly after chemoradiation for Stage III nonsmall cell lung cancer as compared to historical controls.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonsmall Cell Lung Cancer Stage III, Unresectable Non-Small Cell Lung Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Quick Start Durvalumab
Arm Type
Experimental
Arm Description
Standard of care test and procedures for cancer treatments along with Durvalumab treatment at physician's discretion
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Intervention Description
Participants will receive Durvalumab 1500 mg intravenously every two weeks for 60 minutes. Each treatment is called a cycle and lasts for four weeks (or 28 days).
Intervention Type
Other
Intervention Name(s)
the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30)
Intervention Description
Participants will be asked to answer all 30 items on the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30). This patient-reported outcome measure is designed to measure cancer patients' physical, psychological and social functions. The measure can be completed using a paper form, by verbally providing answers to the study team, or by entering the answers online into REDCap using a computer or mobile device. The total time to complete the questionnaire is approximately 11 minutes (
Intervention Type
Diagnostic Test
Intervention Name(s)
COPD Assessment Test (CAT)
Intervention Description
Participants will be asked to answer all items on the COPD assessment test (8 items) and the patient-reported outcome measures designed to measure respiratory function. The measures can be completed using a paper form, by verbally providing answers to the study team, or by entering the answers online into REDCap using a computer or mobile device. The total time to complete the questionnaire is less than 5 minutes.
Intervention Type
Diagnostic Test
Intervention Name(s)
Modified Medical Research Council (mMRC) dyspnea scale
Intervention Description
Participants will be asked to answer the modified medical research council dyspnea scale (1 item), and the patient-reported outcome measures designed to measure respiratory function. The measures can be completed using a paper form, by verbally providing answers to the study team, or by entering the answers online into REDCap using a computer or mobile device. The total time to complete the questionnaire is less than 5 minutes.
Primary Outcome Measure Information:
Title
Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Early Initiation (1-14 days)
Description
Fidelity is defined as a dichotomous composite indicator (yes/no) that describes whether the patient received very early (1-7 days) initiation of Durvalumab as per protocol with all four of the following criteria having been met: (i) CT chest obtained after the last day of radiation therapy and before the first infusion of Durvalumab, (ii) first infusion within 14 days of completing radiation therapy, (iii) second and third doses received within 63 days of the first dose, and (iv) all infusions at least 28 days apart.
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Very Early (1-7 days)
Description
Fidelity is defined as a dichotomous composite indicator (yes/no) that describes whether the patient received very early (1-7 days) initiation of Durvalumab as per protocol with all four of the following criteria having been met: (i) CT chest obtained after the last day of radiation therapy and before the first infusion of Durvalumab, (ii) first infusion within 7 days of completing radiation therapy, (iii) second and third doses received within 63 days of the first dose, and (iv) all infusions at least 28 days apart.
Time Frame
Up to 13 months
Title
Number of Barriers to Initiation of Durvalumab - Very Early (Days 1-7)
Description
Descriptive frequencies of participant survey answers will be examined to conduct qualitative analyses and determine appropriate categories of answers on the free text responses. We will examine barriers/obstacles for everyone in the sample, even those who achieve fidelity; such patients could have experienced delays even if they were still able to achieve fidelity. We will stratify answers/responses by fidelity status.
Time Frame
Up to 13 months
Title
Number of Barriers to Initiation of Durvalumab - Early (Days 8-14)
Description
Descriptive frequencies of participant survey answers will be examined to conduct qualitative analyses and determine appropriate categories of answers on the free text responses. We will examine barriers/obstacles for everyone in the sample, even those who achieve fidelity; such patients could have experienced delays even if they were still able to achieve fidelity. We will stratify answers/responses by fidelity status.
Time Frame
Up to 13 months
Title
Incidences of All Adverse Events
Description
Adverse events, serious adverse events and immune-related adverse events will be tabulated by fidelity status (1-7 days vs. 8-14 days vs. neither) using National Cancer Institute Common Terminology Criteria, version 5.0.
Time Frame
Up to 13 months after intervention
Title
Number of Participants Who Have Immune-Mediated Pneumonitis - Early Fidelity (1-14 days)
Description
Participants with early (1-14 days) fidelity who have immune-mediated early-onset pneumonitis will be estimated and statistically compared in a one-sample test of proportions.
Time Frame
Within 85 days of intervention (Cycles 1-3)
Title
Number of Participants Who Have All-Cause Pneumonitis - Early Fidelity (1-14 days)
Description
Participants with all-cause early-onset pneumonitis among those with early (1-14 days) fidelity and statistically compare it, using a one-sample test of proportions.
Time Frame
Within 85 days of intervention (Cycles 1-3)
Title
Number of Participants to Discontinue Durvalumab Due to Adverse Events
Description
Participants with early fidelity who discontinue Durvalumab at any point due to an adverse event of any cause and compare it using a one-sample test of proportions.
Time Frame
One year
Title
Overall Survival
Description
Using Kaplan-Meier life table methods, overall survival is defined as the number of participants alive at 12 months after the first dose of Durvalumab.
Time Frame
One year
Title
Progression-Free Survival
Description
Using Kaplan-Meier methods, progression-free survival is defined as the number of participants alive and without disease progression as documented by the treating provider at 12 months after the first dose of Durvalumab.
Time Frame
One year
Title
Response Rate
Description
Best objective response rate (ORR) to Durvalumab is defined by either a complete response (CR) or partial response (PR) as per RECIST 1.1 criteria by investigator assessment and confirmed on at least two sequential imaging studies that are at least four weeks apart
Time Frame
One year
Title
Change in Patient-Reported Outcomes Scores (PROs) - European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Version 3
Description
The change in PROs scores from baseline to week 12 using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither). Scale scores range from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
Time Frame
Baseline to 12 weeks after start of intervention
Title
Change in Patient-Reported Outcomes Scores (PROs) - Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) Questionnaire
Description
The QLQ-LC13 includes questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea and site specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. The change in PROs scores from baseline to week 12 using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither). Scale scores range from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
Time Frame
Baseline to 12 weeks after start of intervention
Title
Change in Respiratory Patient Reported Outcomes (PROs) - COPD Assessment Test (CAT)
Description
The COPD Assessment Test (CAT) is a questionnaire for people with Chronic Obstructive Pulmonary Disease (COPD). It is designed to measure the impact of COPD on a person's life and how this changes over time. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD. The change in PROs scores using paired t-tests and compare mean difference scores to the null hypothesis value of zero change to compare between fidelity status (1-7 days vs. 8-14 days vs. neither).
Time Frame
Baseline to 12 weeks after start of intervention
Title
Change in Respiratory Patient Reported Outcomes (PROs) - Modified Medical Research Council (mMRC) Dyspnea Scale
Description
The mMRC (Modified Medical Research Council) Dyspnea Scale is used to assess the degree of baseline functional disability due to dyspnea.The mMRC breathlessness scale ranges from grade 0 to 4 with grade 4 indicating a higher level of respiratory disease severity.
Time Frame
Baseline to 12 weeks after start of intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histological or cytological documentation of nonsmall cell lung cancer that is Stage III according to the American Joint Committee on Cancer Staging Manual, 8th Edition (2017).
Unresectable or medically inoperable as determined by the investigator.
The participant has definitive radiation therapy (e.g., 54 Gy to 66 Gy in 30 to 35 fractions) for lung cancer that is either (a) planned to start within the next 28 days, or (b) currently being administered, or (c) has been completed within the last 14 days.
Platinum-based chemotherapy for lung cancer that is either (a) planned to start within the next 28 days, (b) currently being administered, or (c) has been completed within the last 14 days. Chemotherapy must be for at least two cycles and be administered either before radiation therapy ("induction" or "sequential") or during radiation therapy ("concurrent").
Consolidation Durvalumab is planned for nonsmall cell lung cancer after radiation and chemotherapy.
Eighteen years old or greater.
ECOG performance status of 0-2.
Life expectancy of greater than three months.
Patients with sexual relationships in which either they or their partner may become pregnant must use contraception during the study treatment period.
Ability to understand and be willing to sign an IRB-approved informed consent document directly or via a legally authorized representative.
Exclusion Criteria:
Uncontrolled respiratory symptoms (i.e., cough, dyspnea, fevers, chest pain, or an increase from baseline oxygen requirements) that are interfering with activities of daily living.
Nonsmall cell lung cancer is known to have progressed during radiation therapy.
Nonsmall cell lung cancer is known to have a tumor with a mutation in EGFR associated with sensitivity to first-line therapy with a tyrosine kinase inhibitor (i.e., Ex19del, L858R, EGFR S768I, L861Q, or G719X). If not already known, testing for EGFR mutations is not required for study enrollment.
Prior exposure to an immune checkpoint inhibitor targeting CTLA-4, PD-1, or PD-L1.
Active autoimmune disease requiring systemic immunosuppression at the time of enrollment.
History of autoimmune pneumonitis requiring high-dose systemic steroids (equivalent prednisone >20 mg/day for more than one week).
Uncontrolled intercurrent illness includes ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Patients who are pregnant or breastfeeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Nurse
Phone
3367137748
Email
saverill@wakehealth.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Lycan, MD
Organizational Affiliation
Wake Forest Baptist Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wake Forest Baptist Comprehensive Cancer Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Nurse
Phone
336-713-7748
Email
saverill@wakehealth.edu
First Name & Middle Initial & Last Name & Degree
Thomas Lycan, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Quick Start Durvalumab Following Chemoradiation for Stage III Nonsmall Cell Lung Cancer
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